Pharmacokinetics of estradiol valerate and medroxyprogesterone acetate in different age groups of postmenopausal women

Abstract

Objectives: To study whether ageing affects the pharmacokinetics of estradiol valerate (E 2V) or medroxyprogesterone acetate (MPA) in postmenopausal women. Methods: Forty-six postmenopausal women from two essentially similar pharmacokinetic studies were divided into three age categories: under 60 years ( n=15), between 60 and 65 years ( n=18) and over 65 years ( n=13). They all were treated for 12 days or 14 days with four galenically identical tablets containing combinations of 1 mg or 2 mg E 2V and 2.5 mg or 5 mg MPA. The studies followed an open, randomised cross-over design with no washout between the periods. Serum estradiol and MPA concentrations were measured at steady state on study day 12 or 14 of each period. Results: No statistically significant differences were observed in the peak concentration ( C max), time to peak ( t max), AUC or elimination half-life for estradiol or MPA between the different age groups. In spite of the lack of statistical significance the AUC was on an average 1.6-fold and C max 1.40-fold higher in the oldest group of women than in the youngest group and age was found significant as a continuous variable for AUC and C max for MPA but not for estradiol. Conclusions: The results suggest that there would be no significant changes in the pharmacokinetics of estradiol between women under 60 and over 65 years of age. However, a significant trend towards higher MPA concentrations and bioavailability was observed with increasing age. The results suggest that from the pharmacokinetic point of view the relationship between estradiol and MPA dose to be used in elderly could be different from that in younger postmenopausal women, while no pharmacokinetic reasons to use lower estradiol doses in the elderly were observed.